Alterations of amine neurotransmitter systems (norepinephrine (NE), serotonin (5HT) and dopamine (DA)) have been indirectly implicated in the pathophysiology of the major mental illnesses, depression and schizophrenia. We have applied new techniques to study cerebrospinal fluid (CSF), plasma and urine from drug-free patients with affective illness and schizophrenia using more sensitive and comprehensive characterization of the neurotransmitter systems as well as selective measures of post-synaptic function. New findings include the following: 1. Biopolar (BP) and unipolar (UP) depressed patients now appear to be distinguishable by both presynaptic measures in CSF, plasma and urine (lower levels of NE and/or its metabolite MHPG in BPs) and a post-synaptic measure in blood (higher affinity of beta lymphocyte receptors in BPs, see below). 2. Beta adrenergic receptors in lymphocytes have been characterized in BP, UP, bulemic and anorexic patients as well as controls. The ratio of affinities for two states of the receptor in general parallel plasma NE (not epinephrine) yet can still distinguish groups from one another even when plasma NE does not. 3. Biochemical evidence in man using 5HT and DA metabolites in CSF and in animals using parent amines as well as metabolites points to functional control of DA turnover by 5HT, at least under certain conditions. This has important implications for understanding the role of 5HT function in psychiatric illness. 4. When activity and diet are controlled, the apparent circadian rhythm in plasma MHPG disappears and a robust one in plasma HVA emerges.